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Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Programme changes due to the COVID-19 pandemic have impacted variably on preparation for practice of healthcare professional students. Explanations for such variability need exploration. The aim of our study was to understand what clinical learning, whilst under socially distanced restrictions, worked and why (or why not)., Methods: We conducted a realist evaluation of the undergraduate healthcare programmes at one UK university in 2020-21. Initial programme theories to be tested in this study were derived from discussions with programme leads about the changes they implemented due to the pandemic. Study participants were students and teaching faculty. Online interview transcripts were coded, identifying why interventions had worked or not. This resulted in a set of 'context-mechanism-outcome' (CMO) statements about each intervention. The initial programme theories were refined as a result., Results and Discussion: 29 students and 22 faculty members participated. 18 CMO configurations were identified relating to clinical skills learning and 25 relating to clinical placements. Clinical skills learning was successful whether in person, remote or hybrid if it followed the steps of: demonstration-explanation-mental rehearsal-attempt with feedback. Where it didn't work there was usually a lack of observation and corrective feedback. Placements were generally highly valued despite some deficiencies in student experience. Being useful on placements was felt to be good preparation for practice. If student numbers are to expand, findings about what works in distance learning of clinical skills and the value of various modes of induction to clinical workplace activity may also be relevant post-pandemic., (© 2023. The Author(s).)

Background: Negative faculty role modelling is an area of growing concern especially due to its implications on medical professionalism. The study aims to explore the impacts of negative role modelling on professionalism of medical students in the context of Pakistan., Methods: This qualitative study is part of a larger study exploring impacts of role modelling on professionalism of students. It is based on Constructivist Grounded Theory involving six semi-structured interviews with clinical faculty and three focus group discussions with 22 students. Initial, focused, selective coding and thematic analysis was used to find the core category., Results: Three overarching categories were developed: traits observed with negative role models; impact of negative role modelling; factors promoting negative role modelling. Subcategories of impacts included negative impact on professionalism, emotional impact, and its paradoxical positive impact. Negative role modelling, a manifestation of declining professionalism, was attributed to deteriorating societal values; further compounded by the lack of required mechanisms by institutions and the regulatory authority at their respective levels., Conclusions: In the absence of a strong moral platform at societal level, the burden of responsibility rests with the faculty and more importantly with institutions and regulatory bodies to discourage negative role modelling and educate students to recognize, reflect on and avoid negative behaviours and adopt strong professional values.

Background: Cannabis use is becoming increasingly prevalent worldwide, yet the full spectrum of its effects largely remain unknown. Although cannabis have immunomodulatory properties, there remains a significant gap in our understanding of the potential impact of marijuana use on COVID-19 outcomes. The purpose of this study is to evaluate the effect of chronic cannabis use on severe COVID-19. Materials and Methods: National Inpatient Sample Database was used to sample individuals admitted with the diagnosis of COVID-19. Patients were divided into two groups based on cannabis use. Baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data or age under 18 were excluded. Propensity matching using R was performed to match cannabis users to non-cannabis users 1:1 on age, race, gender, and 17 other comorbidities. The primary outcome was severe COVID-19 infection, defined as a composite of acute respiratory failure, intubation, acute respiratory distress syndrome (ARDS), or severe sepsis with multiorgan failure. Results: Out of 322,214 patients included in the study, 2,603 were cannabis users. Cannabis users were younger and had higher prevalence of tobacco use. On initial analysis, cannabis users had significantly lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. After 1:1 matching, cannabis use was associated with lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. Conclusion: Cannabis users had better outcomes and mortality compared with non-users. The beneficial effect of cannabis use may be attributed to its immunomodulatory effects.

Background/aims: Population surveys are required to measure the prevalence of cataract blindness in the community. We conducted simultaneous surveys in two regions in Malaysia in 2023 to estimate the prevalence of untreated cataract, measure the visual outcomes after cataract surgery and compare the results with the survey in 2014., Methods: The surveys were done in Eastern and Sarawak administrative regions using the rapid assessment of avoidable blindness technique. It involved a multistage cluster sampling method, each cluster comprising 50 residents aged 50 years and older. The prevalence of cataract was determined through a visual acuity (VA) check and eye examination. The VA of those who had undergone cataract surgery was measured, and the findings were compared with the previous survey., Results: A total of 9709 subjects, 50 years old and older, were examined (percentages of response were 94.5% and 96.2% for Eastern and Sarawak, respectively). Comparing the current to the previous survey in 2014, the prevalence of cataract at all levels of surgical thresholds (except unilateral VA <6/60 and <6/18 in the Eastern) was reduced. The percentages of cataract surgery visual outcomes with good VA (6/12) were improved, and those with poor VA (<6/60) were reduced in both regions., Conclusion: There was a reduction in cataract prevalence and improved visual outcomes in both regions. These favourable results could be attributed to the surgical performance monitoring initiatives and the community cataract programme implemented soon after the survey in 2014., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Albumin is commonly used for various indications; however, there is conflicting data regarding its appropriate use in different clinical cases. This study aimed to determine the pattern and appropriateness of albumin use among cancer patients at the King Hussein Cancer Center in Jordan., Methods: A retrospective analysis was conducted on adult cancer patients who were prescribed albumin between January 2019 and July 2020 in both outpatient and inpatient settings. Data collected included demographics, prescribing services, indications and dosing regimens. A literature review was performed using PubMed to assess the appropriateness of albumin indications and dosing regimens against current guidelines, drug information resources and the package insert., Results: Albumin was prescribed to 1,361 patients during the study period. Each patient received an average of 74.4 ± 89 g of albumin for an average of 2.6 ± 1.8 days. Albumin use was deemed appropriate in 69% of the patients. The critical care service accounted for the highest albumin consumption, with 37% of prescriptions for septic shock. Inappropriate use of albumin was most prevalent in the medical solid tumour services (40.8% of prescriptions), primarily for edema (28%)., Conclusion: To the best of the author's knowledge, this study is the first to evaluate albumin use in a large cohort of oncology patients. Approximately one-third of the albumin prescriptions were considered inappropriate. Continuous education on appropriate usage and regular evaluations of guideline adherence are essential to ensure proper utilisation of albumin in cancer care., Competing Interests: CONFLICT OF INTEREST: The authors declare no conflict of interest., (© Copyright 2024, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Background: Crafting quality assessment questions in medical education is a crucial yet time-consuming, expertise-driven undertaking that calls for innovative solutions. Large language models (LLMs), such as ChatGPT (Chat Generative Pre-Trained Transformer), present a promising yet underexplored avenue for such innovations., Aims: This study explores the utility of ChatGPT to generate diverse, high-quality medical questions, focusing on multiple-choice questions (MCQs) as an illustrative example, to increase educator's productivity and enable self-directed learning for students., Description: Leveraging 12 strategies, we demonstrate how ChatGPT can be effectively used to generate assessment questions aligned with Bloom's taxonomy and core knowledge domains while promoting best practices in assessment design., Conclusion: Integrating LLM tools like ChatGPT into generating medical assessment questions like MCQs augments but does not replace human expertise. With continual instruction refinement, AI can produce high-standard questions. Yet, the onus of ensuring ultimate quality and accuracy remains with subject matter experts, affirming the irreplaceable value of human involvement in the artificial intelligence-driven education paradigm.

Background: Device-related infective endocarditis (IE) is associated with high mortality, resulting in a growing emphasis on identifying and managing comorbidities that increase the risk of IE in these patients. Psoriasis is increasingly being recognized as having multiple cardiovascular manifestations. However, little is known about the impact of psoriasis on IE risk in patients with permanent pacemakers (PPM). Our study aimed to assess whether psoriasis is associated with an increased risk of developing IE in patients with PPM., Methods: The National Inpatient Sample database was utilized to extract patients with PPM. The presence of psoriasis stratified patients. Demographic and comorbidity data were collected. 1:10,000 propensity matching for IE risk factors was performed to examine independent associations between psoriasis and IE., Results: Of 437,793 patients, 45 had psoriasis. Psoriasis patients had higher IE rates (4.4% vs. 0.6%; P < 0.01). On multivariate analysis, psoriasis was associated with a 7.2-fold high IE risk (OR: 7.2 [1.7-30.2]; P < 0.01). Post-match analysis showed an 8.3-fold IE risk in psoriasis patients (OR: 8.3 [2.0-34.4]; P < 0.001)., Conclusion: Psoriasis was independently associated with elevated IE risk in patients with PPM. Further studies are required to corroborate these findings, which will have implications for IE prophylaxis., (© 2024 the International Society of Dermatology.)

Introduction: Stroke, a leading cause of morbidity and mortality globally, demands heightened awareness and knowledge for effective preventive strategies and tailored response. Sudan is classified as a low income country with a low rate of literacy, lack of knowledge, and awareness about diseases. Thus, this study aimed to assess stroke awareness and knowledge among Sudanese population, and identify the associated factors influencing awareness., Methods: A cross-sectional study conducted between October and November 2022 through a self-administered online survey distributed via various social media platforms. The study involved adults aged 18 years and above through snow-ball sampling technique. The survey covered general awareness and knowledge concerning stroke risk factors, consequences, and the appropriate responses taken during acute stroke attacks., Results: A total of 410 participants were enrolled in the study, majority (93.4%) were from urban area and had university degree (92.4%). Furthermore, 92.2% were aware about stroke and 74.9% were able to recognize the symptoms of stroke. Only 40.2% identified all correct answers, 96.3, 92.3, and 95.1% recognized at least one risk factor, early symptom, and consequences, respectively. Females were significantly more than males able to identify at least one risk factor. Almost all participants (99.5%) perceived stroke as a serious disease (99.5%). Notably, 86.3% would promptly transport a suspected stroke patient to the hospital. The multivariable analysis showed that females versus males and patients with depression versus without depression had significantly higher odds to identify at least one risk factor (OR of 14.716 [95% CI 1.901; 113.908] and 0.241 [95% CI 0.059; 0.984], respectively)., Conclusion: The study concluded that stroke knowledge and awareness among Sudanese population is suboptimal. Furthermore, early stroke recognition and intake of the appropriate management strategies are lacking which highlights the need for targeted education and awareness campaigns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eltayib, Jirjees, Suliman, AlObaidi, Ahmed, Kharaba, Alfoteih, Barakat, Khidhair, ALSalamat, Mustafa, Cherri, El Khatib, Hallit, Malaeb and Hosseini.)

Introduction: Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications., Method: A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison., Results: Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes., Discussion: Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tetraalkylammonium salt (TAS) is an organic salt widely employed as a precursor, additive or electrolyte in solar cell applications, such as perovskite or dye-sensitized solar cells. Notably, Perovskite solar cells (PSCs) have garnered acclaim for their exceptional efficiency. However, PSCs have been associated with environmental and health concerns due to the presence of lead (Pb) content, the use of hazardous solvents, and the incorporation of TAS in their fabrication processes, which significantly contributes to environmental and human health toxicity. As a response, there is a growing trend towards transitioning to safer and biobased materials in PSC fabrication to address these concerns. However, the potential health hazards associated with TAS necessitate a thorough evaluation, considering the widespread use of this substance. Nevertheless, the overexploitation of TAS could potentially increase the disposal of TAS in the ecosystem, thus, posing a major health risk and severe pollution. Therefore, this review article presents a comprehensive discussion on the in vitro and in vivo toxicity assays of TAS as a potential material in solar energy applications, including cytotoxicity, genotoxicity, in vivo dermal, and systemic toxicity. In addition, this review emphasizes the toxicity of TAS compounds, particularly the linear tetraalkyl chain structures, and summarizes essential findings from past studies as a point of reference for the development of non-toxic and environmentally friendly TAS derivatives in future studies. The effects of the TAS alkyl chain length, polar head and hydrophobicity, cation and anion, and other properties are also included in this review., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Adrenal hemorrhage (AH) can occur due to multiple etiologies with variable radiographic appearance, often indistinguishable from underlying adrenal neoplasms. There is a lack of AH literature and evidence-based guidelines. Our study aimed to understand the prevalence and etiology of AH, follow-up, and incidence of underlying neoplasm., Methods: An institutional database was queried from January 2006 to October 2021 for patients with AH on imaging, excluding patients with known malignancies, adrenal masses, or prior adrenal surgery. Demographics, medical history, hematoma size, laterality, biochemical evaluation, intervention, and additional imaging were reviewed., Results: Of 490,301 imaging reports queried, 530 (0.11%) with AH met inclusion criteria. Most imaging (n = 485, 91.5%) was performed during trauma evaluation. Two patients underwent dedicated intervention at presentation. Interval imaging was performed in 114 (21.5%) patients at a median of 2.6 (interquartile range 0.99-13.4) mo, with resolution (n = 84, 73.7%) or decreased size of AH (n = 21, 18.4%) in most patients. Only 10 patients (1.9%) saw an outpatient provider in our system to address AH or evaluate for underlying mass, and 9 (1.7%) underwent biochemical screening. Thirteen patients (11% of 118 patients with any follow-up) had evidence of an adrenal mass, confirmed on serial imaging (n = 10) or adrenalectomy (n = 3). Scans performed for nontrauma indications were significantly more likely to have an underlying mass (n = 6/26 [23.1%]) than those performed for trauma evaluation (n = 7/92 [7.6%], P = 0.04)., Conclusions: AH is a rare finding associated with an increased rate of underlying adrenal mass, particularly when unrelated to trauma. Most AH resolves spontaneously without intervention. Follow-up imaging at 6 mo can help distinguish mass-associated AH from simple hemorrhage., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Metabolic-associated fatty-liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most widespread and emerging chronic liver disease worldwide, with increasing prevalence rates also in the Asia-Pacific region. The disease has a high socio-economic burden as it negatively impacts the finances and quality of life of individuals affected and has a major burden on healthcare systems. The most important pathological event in MAFLD aetiopathogenesis is oxidative stress, which leads to functional and structural abnormalities in the liver as well as being involved in the development of other concomitant cardiometabolic diseases. MAFLD is a rather complex multisystemic clinical condition involving liver damage and a wide spectrum of extrahepatic manifestations such as obesity, type 2 diabetes, metabolic syndrome and cardiovascular diseases. This complexity requires the cooperation of multiple experts to identify MAFLD at an early stage, treat associated comorbidities, and promptly refer the patient to the hepatologist when needed. This review summarizes the current knowledge about MAFLD and reports the opinion of a group of experts on the increasing prevalence and burden of the disease in the southeast Asia region, the current journey of patients with MAFLD in developing countries, the role of oxidative stress and antioxidant treatment, and the importance of a multidisciplinary approach for early diagnosis and disease management. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special&#95;issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series., Competing Interests: Disclosure and potential conflicts of interest: FA: Speaker fee for webinars from Viatris. DP: Speaker fee from SV More, Echosens, Inopgen, Otsuka, Biocare, Zuellig, Gilead. RAR: Received grant for research support from Viatris via Navistas Healthcare. Speaker fee from Mylan, Pfizer, Ferring, AbbVie. NM: None. NT: Speaker fee for Viatris, Zuellig Pharma, Novartis, Abbot. RC: Speaker fee for Roche. CB: Speaker fee from Takeda, Viatris, Sandoz, Thai-Otsuka. AS: None. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/12/dic.2023-9-3-COI.pdf, (Copyright © 2024 Angelico F, Alcantara-Payawal D, Rani RA, Mustafa N, Thongtang N, Chaiteerakij R, Bunchorntavakul C, Sukonthasarn A.)

Aim: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022., Methods: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine)., Results: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics., Conclusions: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal., Competing Interests: LLL report receiving grants through her affiliated institutions and/or honoraria for consultancy and speaker bureau from Abbott, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi, Servier, and Zuellig Pharma. SPC report receiving the research grant through her affiliated Society (Malaysian Endocrine and Metabolic Society) and honoraria for consultancy and speaker bureau from Abbott, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Roche, Sanofi, Servier, and Zuellig Pharma. KR and PS are employee of Boehringer Ingelheim. Other co-authors declared no potential conflict of interest. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The treat-to-target serum uric acid approach is recommended in local and international guidelines on gout management. Instruction for initiation and dose escalation for urate lowering therapy may cause confusion to the patient. Our aim was to develop and validate Gout Treat-To- Target booklet to aid in patient education., Materials and Methods: A content development team which consisted of three consultant rheumatologists developed the booklet. Content validation was performed by a panel of evaluators consisted of eleven physicians (four consultant rheumatologists, two clinical specialists, and five medical officers), who were involved in gout management. Face validation was performed by ten patients with gout., Results: Item-Content Validity Index ranged from 0.9 to 1 with regards to relevancy, clarity, ambiguity and simplicity. Side effects of uricosuric agents were added to the draft based on an evaluator's comment. Item-Face Validity Index was 1, which indicated that all patients were in 100% agreement with all items., Conclusion: We developed and validated our Gout Treat-to- Target booklet. There was high agreement in I-FVI and I-CVI among physicians and patients.

Introduction: Salmonella typhi could infect the intestinal tract and the bloodstream or invade body organs and secrete endotoxins. It is endemic in developing countries. It is increasingly evolving antimicrobial resistance to several commonly used antimicrobial agents., Materials and Methods: A cross-sectional study was done at Iraqi Communicable Disease Control Center, where all confirmed cases of Salmonella typhi are reported, for a period 2019-2021. All demographic, epidemiological and clinical characteristics of patients, comorbidities, type of samples, distribution of S. typhi by age and gender, time distribution in each year and profile of bacterial resistance and sensitivity to antibiotics were gathered and analysed., Results: Most samples were taken from blood. The mean age of cases during 2019, 2020 and 2021 was 18.7 ± 6.5, 17.7 ± 14.1 and 17.3 ± 12.8. Males constituted 56.7%, 58.5% and 39.8%, respectively. Some cases had comorbidities. Most cases had headache and fever. Some of them had nausea, diarrhoea, vomiting and epigastric pain. The age and sex were significantly associated with years of reporting. The most months of case reporting were June-July (2019 and 2021), Jan. -Feb. (2020). There was an obvious increase in S. typhi resistance to ceftriaxone (92.2%, 86.1%, 88.8%) and ampicillin (77.1%, 76.9%, 81.27%). There was a gradual increase in sensitivity to tetracycline (83.1%, 88.1%, 94%), cotrimoxazole (86.7%, 86.1%, 92.2%), ciprofloxacin (78.3%, 90.1%, 87.8%) and cefixime (77.7%, 72.3%, 72.7%)., Conclusions: There was a sharp rise in resistance rates of the S. typhi in Iraq (during 2019-2021) to ceftriaxone and ampicillin, while there were highest sensitivity rates to imipenem, aztreonam and chloramphenicol. The following recommendations were made: (1) Improvement of general hygiene and food safety measures. (2) Emphasis on vaccination and surveillance of Salmonella infection. (3) Rational use of appropriate antibiotics through implementation of treatment guidelines. (5) Educate communities and travelers about the risks of S. typhi and its preventive measures.

Background: Persistent pelvic pain is pain sensed in or around the pelvis and is often associated with negative cognitive, behavioral, sexual, and emotional consequences. The lack of interprofessional persistent pelvic pain management programs that address the complex interplay of biopsychosocial factors result in lengthy wait times and negative health outcomes. Limited access to evidence informed self-management educational resources contributes to poor coping strategies. Evidence shows that self-management education and strategies support patients while they wait for care. However, very few studies explore the patient's lived experience of participating in an online educational program designed for persistent pelvic pain., Objectives: This study aims to understand the experience of women with persistent pelvic pain participating in an online, self-management education program ("Pelvic Pain Empowered Management" program) while awaiting care at an interprofessional pelvic pain clinic., Design: A descriptive qualitative approach was used to explore the experiences of women participating in an online educational program designed for cis women with persistent pelvic pain., Methods: We conducted semi-structured interviews with 11 women, transcribed the data verbatim using NVivo software (NVivo 12, QSR International Pty Ltd.), and analyzed inductively using previously established methods., Results: We identified four main themes relevant to women's experiences of the program: (1) the program shaped expectations around upcoming pelvic pain appointments, (2) the program content is relevant and resonates with people with lived experience of persistent pelvic pain, (3) the program enhanced understanding of persistent pelvic pain, and (4) the program empowered people with skills and strategies to better manage their persistent pelvic pain., Conclusion: Our findings highlight how self-directed online patient education can be leveraged while persistent pelvic pain patients wait for care to support them in setting expectations around care and in engaging in pain self-management.

There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ +/- . The 3xTgAD/Polβ +/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ +/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD., Competing Interests: Conflict of Interest Statement V.A.B. had a material CRADA agreement with ChromaDex, Inc.

Purpose: The complications of type 2 diabetes (T2DM) have a negative impact on health-related quality of life (HRQoL) and could lead to increased healthcare costs. However, there is a lack of evidence regarding how and to what extent T2DM complications, particularly macrovascular and microvascular complications, affect the patients' HRQoL. This study aimed to evaluate the HRQoL in relation to diabetes complications and identify associated factors among patients with T2DM., Methods: A cross-sectional study was conducted over six months on T2DM patients at a National University Hospital, Malaysia. Since Malaysia is a multiethnic country with majority Malay-speaking and English widely used, the Malay and English versions of the revised version Diabetes Quality of life (DQoL) questionnaire was used to measure HRQoL. Multiple Linear Regression was applied to estimate association of individual DQoL domains with T2DM-related complications, sociodemographic and clinical characteristics., Results: A total of 513 patients were recruited in the study. Sociodemographic (age, gender, ethnicity, employment, education) and body mass index affected satisfaction, impact and worry domains while complications affected the impact domain. Poorer HRQoL were demonstrated for severe stages heart failure (p = 0.001), nephropathy (p = 0.029), retinopathy (p < 0.001). The presence of neuropathy (p = 0.004) and foot ulcer (p = 0.039) showed poor HRQoL regardless of severity stage. Increase frequencies of hypoglycaemia (p < 0.001) showed poorer HRQoL compared to those with lesser frequencies., Conclusion: The complications, sociodemographic and clinical characteristics of patients with T2DM affect the HRQoL domains differently. Understanding the point of which complication types and stages impact HRQoL the most can provide insights to clinicians to prioritise on effective interventions. The study findings may assist researchers and policymakers in selecting appropriate health state values when conducting cost-effectiveness studies to aid decision making., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Cigarette smoking acknowledged as the foremost contributor to preventable illnesses and deaths, has steadily risen since its inception, evolving into a global health crisis of paramount significance, particularly within the context of medical students who represent the future healthcare workforce. This study, conducted at Quaid-e-Azam Medical College, Bahawalpur, aimed to comprehensively evaluate current students' knowledge, attitudes, and practices concerning cigarette smoking. Employing a web-based cross-sectional observational descriptive study design over the study period from June 15, 2020, to August 1, 2020, a sample of 200 medical students drawn from the first to fifth year was examined using stratified sampling. Data collection involved the distribution of a meticulously designed and pre-tested questionnaire through social media platforms, encompassing inquiries about participants' biodata and research-related topics. The subsequent data analysis utilized Google Spreadsheets, Microsoft Excel, Microsoft Word, and SPSS software to calculate percentages, create graphical representations, construct tables, and apply the chi-square test. The survey findings illuminated a remarkably high level of awareness, with 99% of respondents recognizing the harmful effects of smoking, including elevated cancer risk, and 94% acknowledging its addictive nature. A substantial 93% regarded passive smoking as equally detrimental as active smoking. In comparison, 98.5% were aware of the heightened risk of respiratory illnesses in children exposed to smoking. The majority exhibited a responsible stance towards discouraging smoking, with 90.5% feeling a duty to encourage cessation and 71.5% considering maintaining good health a sufficient incentive to quit. Additionally, 97% concurred that smoking in the presence of children should be avoided. Concerning smoking cessation, 64.5% believed high taxes were effective, and 97.5% deemed public smoking bans effective measures. Notably, 74% thought professional advice had limited influence on a smoker's attitude. Active smokers constituted a mere 20% of the sample, with a mere 2% commencing smoking before age 16 and 10% succumbing to peer pressure or media influence as instigating factors. Furthermore, 13.5% reported exam-related anxiety as a trigger for smoking, and 10% admitted to smoking in the company of non-smokers. Encouragingly, 19.5% expressed a desire to quit, with 5% seeking professional guidance in their cessation attempts. In conclusion, most participants exhibited commendable knowledge and a positive attitude towards cigarette smoking, contributing to a low prevalence of tobacco consumption among them. Nevertheless, the study underscores the need for ongoing improvements through targeted educational initiatives and governmental regulations to further mitigate tobacco use among future healthcare professionals and the broader population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mustafa et al.)

Background: No large-scale studies have compared associations between body composition and cardiovascular risk factors across multi-ethnic populations., Methods: Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c., Results: Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m 2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men; but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c., Conclusion: There were distinct patterns of adiposity and body composition and cardiovascular risk factors across ethnic groups. We need to better understand the mechanisms relating body composition with cardiovascular risk to attenuate the increasing global burden of obesity-related disease., (© 2023. The Author(s).)

Purpose: Chronic pain affects 1 in 4 Canadians and is a leading contributor of disability. Although virtual care has become more prevalent, it is unclear how adults living with chronic pain perceive virtual delivery of exercise interventions within multidisciplinary chronic pain clinics (MCPC). This study explores the perspectives of adults living with chronic pain regarding their perceived barriers and facilitators and recommendations when implementing virtual care exercise interventions within MCPCs., Methods: We conducted an interpretive description qualitative study based on semi-structured interviews with adults (age ≥18 years) living with chronic pain from a MCPC in Toronto, Canada, between March 1 and April 30, 2021., Results: We completed fifteen ( N  = 15) interviews of adults living with chronic pain. We identified eight themes that addressed the study objectives: 1) virtual care supplements in-person care, 2) virtual care improves accessibility, 3) impact of technology on participation, 4) navigating the home environment, 5) impact of pain on participation, 6) impact of supervision and feedback, 7) the need for tailored care, and 8) the need for preparation and additional support., Conclusion: Our results reveal that adults living with chronic pain view virtual care exercise interventions positively however, the implementation of these interventions must be carefully considered within MCPCs. Specifically, virtual care was considered an excellent adjunct to in-person care but should not replace it completely.Implications for RehabilitationChronic pain is a leading contributor of disability.Exercise interventions are recommended component of comprehensive pain management.Virtual delivery of exercise interventions are becoming more prevalent.Adults living with chronic pain view virtual care exercise interventions positively as they can supplement in-person care and improve access to this type of care.

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The Ikaros zinc-finger transcription factor Eos has largely been associated with sustaining the immunosuppressive functions of regulatory T cells. Paradoxically, Eos has more recently been implicated in promoting proinflammatory responses in the dysregulated setting of autoimmunity. However, the precise role of Eos in regulating the differentiation and function of effector CD4+ T cell subsets remains unclear. In this study, we find that Eos is a positive regulator of the differentiation of murine CD4+ TH2 cells, an effector population that has been implicated in both immunity against helminthic parasites and the induction of allergic asthma. Using murine in vitro TH2 polarization and an in vivo house dust mite asthma model, we find that EosKO T cells exhibit reduced expression of key TH2 transcription factors, effector cytokines, and cytokine receptors. Mechanistically, we find that the IL-2/STAT5 axis and its downstream TH2 gene targets are one of the most significantly downregulated pathways in Eos-deficient cells. Consistent with these observations, we find that Eos forms, to our knowledge, a novel complex with and supports the tyrosine phosphorylation of STAT5. Collectively, these data define a regulatory mechanism whereby Eos propagates STAT5 activity to facilitate TH2 cell differentiation., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Discarded polymeric or ceramic membranes are currently in need of appropriate and sustainable management. In the present study, the direct reuse of discarded ceramic membranes in membrane contactor (MC) systems for CO 2 removal was investigated for the first time. The hydrophobic surface modification of the discarded ceramic membrane was done by using macromolecule additive coating. The influence of operational parameters (absorbent liquid flow rate ( Q L ), feed gas flow rate ( Q g ), and different NaOH concentrations) of the MC on CO 2 removal was investigated to prove the technical feasibility of reused ceramic membranes. The CO 2 absorption flux was 7.9 × 10 -4 mol/m 2 s at optimal conditions of 2 M NaOH, Q L (20 mL/min), and Q g (300 mL/min) with a removal efficiency of 98%, which lasted for 8 h. This study demonstrates a potential alternative for the reuse of discarded ceramic membranes and avoids their disposal in landfills. The proposed approach will also bring membrane technology into the circular economy and achieve sustainability goals by reducing the amount of waste from discarded ceramic membranes in the future and combating global warming by absorbing CO 2 ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: There is a knowledge gap of health utility values for Type 2 Diabetes Mellitus (T2DM) complications in Malaysia. This study aimed to estimate EQ-5D-5L utility values and evaluate health-related quality of life (HRQoL) for Malaysian T2DM associated with complications and clinical characteristics., Methods: A cross-sectional study was conducted on T2DM patients at a tertiary hospital outpatient using the Malay and English version of the EQ-5D-5L questionnaire. Health utility values were derived using the Malaysian EQ-5D-5L value set. Ordinary least squares (OLS) multivariable regression model was used to estimate the health utility decrements associated with T2DM-related complications and clinical characteristics., Results: A total of 513 T2DM patients were recruited. Overall, pain was the most affected of all five EQ-5D-5L dimensions. Patients with foot ulcer, amputation, severe heart failure and frequent hypoglycemia reported more problems collectively in all EQ-5D-5L dimensions. Older age, lower education level, longer duration of T2DM, urine protein creatine index (UPCI) > 0.02 g/mmol, and injection therapy were significantly associated with lower EQ-5D-5L utility values (p < 0.004, Bonferroni adjusted). The lowest unadjusted utility values were reported for severe heart failure 0.65 (interquartile range, IQR 0.50), frequent hypoglycemia 0.74 (0.22) and being amputated 0.78 (0.47). In the multivariable regression model after controlling for sociodemographic and clinical characteristics, the largest utility value decrement was observed for amputation (- 0.158, SE 0.087, p = 0.05), frequent hypoglycemia (- 0.101, SE 0.030, p = 0.001), myocardial infarction (-0.050, SE 0.022, p = 0.022) and obesity (-0.034, SE 0.016, p = 0.029)., Conclusion: Larger utility value decrements were found for severe stages of complications. These findings suggest the value of defining severity of complications in utility elicitation studies. The utility decrement quantified for different T2DM complication severity will be useful for economic evaluations within diabetic-related fields., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Senescence is a natural phenomenon of growing old. It accelerates under certain conditions like diabetes mellitus resulting in early decline of bodily functions, which can be avoided by many claimed functional foods. The present study aims to investigate the anti-aging ability of Fenugreek seeds ( Trigonellafoenum-graecum) ; a common ingredient of Indo-Pak cuisines. Briefly, the Fenugreek seeds extract (FgSE) in concentrationsof0.1, 0.5 and 1 mg/ml inhibited the formation of Advanced Glycation End products (AGEs) and fructosamine adducts in Bovine serum albumin (BSA)/fructose model in vitro . The BSA conformational analysis via Circular Dichorism and Congo red assays showed that it preserves secondary structure of BSA in aforementioned model. Although mechanistic studies revealed insignificant lysine blocking ability of Fenugreek by OPA assay, however carbonyl entrapping was found to be 24%, 34% and 42% at 0.1, 0.5 and 1 mg/ml, respectively. In vivo model of High Fructose diet (HFD) induced glycation, FgSE treatment in doses of 10, 25 & 50 mg/kg markedly improved Escape latency (p < 0.01) and preserved cognition in Morris Water Maze. Our data further exhibits significant decrease of CML ( N ε-carboxymethyl lysine) levels in serum and hippocampus byFgSE treatment in comparison with HFD group. Therefore, we deduced that FgSE prevents glycation-induced memory decline via entrapping the reactive carbonyl intermediates, formed during production of AGEs. Hence, as a promising functional food it slows down the harmful process of glycation and aging associated morbidities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: The prevalence of non-adherence to antidiabetic treatment remains high despite various efforts. Thus, the positive effects of the antidiabetic treatment cannot be optimised and the disease progresses to complications. This present systematic review and meta-analysis aimed to evaluate the effects of mobile applications (apps) intervention on medication adherence and type 2 diabetes mellitus (T2DM) control., Methods: This research was conducted following the PRISMA guidelines. The databases that had been searched included Web of Science, PubMed, Scopus, Cochrane Library and Ovid from 2017 to 2022. Study characteristics were retrieved and study outcomes such as adherence status and diabetes control were extracted and quantitatively analysed through meta-analysis., Results: Eight studies met the final inclusion criteria and were included in the analysis, contributing to a total of 884 subjects. The methodological quality of the included studies was variable. Three studies reported statistically significant improvement in medication adherence through mobile apps intervention. Additionally, the mobile apps intervention proved effective in reducing glycaemic outcomes. As compared to non-mobile apps users, glycated haemoglobin (HbA1c) significantly decreased by 0.36% (95% CI -0.47% to -0.25%), whereas fasting plasma glucose (FPG) significantly decreased by 16.75 mg/dL (95% CI -17.60 mg/dL to -15.80 mg/dL)., Conclusion: Mobile apps intervention had beneficial impacts on medication adherence and glycaemic parameters. Future research should explore the best practical approach for real-world settings.

To observe trends of diabetes and its associated risk factors from health surveys 2002-2017 in rural areas of Baluchistan-Pakistan and a secondary analysis based on community based health surveys of Baluchistan conducted between 2001-02, 2009-10, and 2016-17. A total of 4250 participants were included in this combined analysis, 2515 from 2001-2002, 1377 from 2009-2010 and 358 from 2016-2017 survey year. In each survey, detailed information of baseline parameters were noted on a predesigned questionnaire. Fasting plasma glucose (FPG) was used for diagnosis of diabetes for comparative purposes in this analysis. Cardiovascular (CVD) risk factors including hypertension, obesity, dyslipidaemia, tobacco use, alcohol consumption, and physical activity were compared. Most subjects were aged 30-50 years and males were found higher in 2016-17 compared to 2001-02 and 2009-10. Pronounced increases in BMI, waist circumference, blood pressure, and family history of diabetes were observed in 2016-17. Diabetes prevalence was 4.2 (3.4-4.9), 7.8 (6.6-9.2) and 31.9 (26.9-37.4), whilst pre-diabetes was 1.7 (1.3-2.2), 3.6 (2.8-4.6) and 10.7 (7.6-14.9) in years 2001-02, 2009-10, and 2016-17, respectively. Among those aged 20-39years, prevalence of diabetes was stable from 2001-10 yet increased considerably between the ages of 30-39years in 2016-17. Throughout the observed period, rapid increases were observed in hypertension, obesity, and dyslipidaemia, however, addiction to tobacco use and alcohol intake decreased. Adjusted odd ratios showed age, marital status, education, hypertension, and family history of diabetes as associated risk factors for glycaemic dysregulation. The rural Baluchistan population is confronted with increasing trends of early onset diabetes due to highly associated CVD risk factors, especially central obesity and dyslipidaemia, raising a major public health challenge., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abdul Basit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Antibody-mediated rejection (AMR) still persists as the major hurdle towards successful renal allograft survival. This paper aims to report on the HLA antibody landscape of renal transplant candidates in Malaysia. A total of 2,219 adult samples from 2016 to 2019 were analysed for anti-HLA antibodies using solid-phase assay. Our findings highlight the prevalence and risk factors for antibodies against HLA antigens in renal transplant settings, which could be beneficial for selecting compatible recipients from deceased organ donors. To the best of our knowledge, this study is the first to demonstrate that ethnic Malay and Chinese showed significantly higher prevalence of anti-HLA antibodies. Based on our multivariate analysis: (i) female gender was associated with higher risk for panel reactive antibodies (PRAs) against Class I, Class II, and Class I and II (p < 0.001); (ii) older patients (≥ 38 years old) were associated with higher risk of positivity against Class I, Class II and Class I and II (p < 0.001); (iii) Malays showed significant association with Class II antibodies (p = 0.035); Chinese patients presented with higher risk of PRA positivity against Class II (p < 0.001) and Class I and II (p = 0.01); Indians were significantly associated with higher risk of HLA antibody sensitization against Class I (p = 0.022), Class II (p = 0.026) and Class I and II (p = 0.05). Thus, our findings suggested that female gender, older age (≥ 38 years old) and ethnicity may serve as independent risk factors for HLA antibody sensitization in adult renal transplant candidates., (© 2023. The Author(s).)

Malfunctions in the immune system cause multiple sclerosis (MS), which initiates mild to severe nerve damage. MS will disturb the signal communication between the brain and other body parts, and early diagnosis will help reduce the harshness of MS in humankind. Magnetic resonance imaging (MRI) supported MS detection is a standard clinical procedure in which the bio-image recorded with a chosen modality is considered to assess the severity of the disease. The proposed research aims to implement a convolutional neural network (CNN) supported scheme to detect MS lesions in the chosen brain MRI slices. The stages of this framework include (i) image collection and resizing, (ii) deep feature mining, (iii) hand-crafted feature mining, (iii) feature optimization with firefly algorithm, and (iv) serial feature integration and classification. In this work, five-fold cross-validation is executed, and the final result is considered for the assessment. The brain MRI slices with/without the skull section are examined separately, presenting the attained results. The experimental outcome of this study confirms that the VGG16 with random forest (RF) classifier offered a classification accuracy of >98% MRI with skull, and VGG16 with K-nearest neighbor (KNN) provided an accuracy of >98% without the skull., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Sujatha Krishnamoorthy et al.)

Plant extract-based green synthesis of nanoparticles is an emerging class of nanotechnology that has revolutionized the entire field of biological sciences. Green synthesized nanoparticles are used as super-growth promoters and antifungal agents. In this study, selenium nanoparticles (SeNPs) were synthesized using Melia azedarach leaves extract as the main reducing and stabilizing agent and characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray (EDX), and fourier transform infrared spectrometer (FTIR). The green synthesized SeNPs were exogenously applied on Mangifera indica infected with mango malformation disease. The SeNPs at a concentration of 30 μg/mL were found to be the best concentration which enhanced the physiological (chlorophyll and membrane stability index), and biochemical (proline and soluble sugar) parameters. The antioxidant defense system was also explored, and it was reported that green synthesized SeNPs significantly reduced the biotic stress by enhancing enzymatic and non-enzymatic activities. In vitro antifungal activity of SeNPs reported that 300 μg/mL concentration inhibited the Fusarium mangiferae the most. This study is considered the first biocompatible approach to evaluate the potential of green synthesized SeNPs to improve the health of mango malformation-infected plants and effective management strategy to inhibit the growth of F. mangifera., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shahbaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Glioblastoma (GBM) has a very poor prognosis despite current treatment. We previously found cytotoxic synergy between the AURKA inhibitor alisertib and the CNS-penetrating taxane TPI 287 against GBM tumor cells in vitro., Methods: We used an orthotopic human GBM xenograft mouse model to test if TPI 287 potentiates alisertib in vivo. Western blotting, immunohistochemistry, siRNA knockdown, annexin V binding, and 3-dimensional Matrigel invasion assays were used to investigate potential mechanisms of alisertib and TPI 287 treatment interactions., Results: Alisertib + TPI 287 combination therapy significantly prolonged animal survival compared to vehicle (p = 0.011), but only marginally compared to alisertib alone. Alisertib, TPI 287, and combined alisertib + TPI 287 reduced animal tumor volume compared to vehicle-treated controls. This was statistically significant for the combination therapy at 4 weeks (p < 0.0001). Alisertib + TPI 287 treatment decreased anti-apoptotic Bcl-2 protein levels in vivo and in vitro. Expression of the pro-apoptotic protein Bak was significantly increased by combination treatment (p < 0.0001). Pro-apoptotic Bim and Bak knockdown by siRNA decreased apoptosis by alisertib + TPI 287 in GB9, GB30, and U87 cells (p = 0.0005 to 0.0381). Although alisertib and TPI 287 significantly reduced GBM cell invasion (p < 0.0001), their combination was no more effective than TPI 287 alone., Conclusions: Results suggest that apoptosis is the dominant mechanism of potentiation of GBM growth inhibition by alisertib + TPI 287, in part through effects on Bcl-2 family proteins, providing a rationale for further laboratory testing of an AURKA inhibitor plus TPI 287 as a potential therapy against GBM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Olfactory impairment may be present among patients with coronavirus disease 2019 self-perceived as asymptomatic. This study aimed to assess olfactory function among these individuals., Methods: A cross-sectional study involving patients with coronavirus disease 2019 self-perceived as asymptomatic was conducted. Assessments included the subjective Malaysian Smell and Taste Questionnaire and the culturally adapted Malaysian version of the objective Sniffin' Sticks Identification smell test., Results: In 81 participants (mean age of 31.59 ± 12.04 years), with mean time from diagnosis to smell test of 7.47 ± 3.79 days, subjective assessment showed that 80.2 per cent were asymptomatic (questionnaire score of 6) and 19 per cent had mild symptoms (questionnaire score of 7 and 8). The mean objective smell test score was 10.89 ± 2.11. The prevalence of olfactory impairment was 76.6 per cent among patients with coronavirus disease 2019 self-perceived as asymptomatic. There was no association between the questionnaire and the smell test scores ( p = 0.25). There was a correlation between the smell test score and the duration from diagnosis to smell test ( p = 0.04)., Conclusion: The objective assessment demonstrated that coronavirus disease 2019 patients who perceived themselves as asymptomatic showed olfactory impairment.

Prediction model has been the focus of studies since the last century in the diagnosis and prognosis of various diseases. With the advancement in computational technology, machine learning (ML) has become the widely used tool to develop a prediction model. This review is to investigate the current development of prediction model for the risk of cardiovascular disease (CVD) among type 2 diabetes (T2DM) patients using machine learning. A systematic search on Scopus and Web of Science (WoS) was conducted to look for relevant articles based on the research question. The risk of bias (ROB) for all articles were assessed based on the Prediction model Risk of Bias Assessment Tool (PROBAST) statement. Neural network with 76.6% precision, 88.06% sensitivity, and area under the curve (AUC) of 0.91 was found to be the most reliable algorithm in developing prediction model for cardiovascular disease among type 2 diabetes patients. The overall concern of applicability of all included studies is low. While two out of 10 studies were shown to have high ROB, another studies ROB are unknown due to the lack of information. The adherence to reporting standards was conducted based on the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) standard where the overall score is 53.75%. It is highly recommended that future model development should adhere to the PROBAST and TRIPOD assessment to reduce the risk of bias and ensure its applicability in clinical settings. Potential lipid peroxidation marker is also recommended in future cardiovascular disease prediction model to improve overall model applicability., (© 2023. The Author(s).)

The relationship between environmental strategy and environmental performance has been extensively analyzed in the environmental management literature. However, this relationship is spurious due to the inconsistence outcomes, lack of intervening mechanism, and scarcity of appropriate context. This study undertakes these considerations by exploring the underlying moderation-mediation mechanism through which proactive corporate environmental strategy affects corporate environmental performance. The hypotheses of the study were empirically tested on the data gathered from 147 ISO 14001:2015 certified firms in Pakistan. The data was statistically validated and then tested with Bootstrapping method using Preacher and Hayes Process Macros. The findings of the study revealed that a proactive corporate environmental strategy predicts corporate environmental performance through green product innovation. Moreover, the moderation hypothesis of the organizational structure variable in the nexus between proactive corporate environmental strategy and green product innovation was not supported in the full sample, whereas the split sample based on organizational size indicated moderation effects in the small firm's sample. The findings of the study carry important implications for firms related to corporate environmental strategy and green product innovation strategy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study compared the pharmacokinetics (PK) of the ravulizumab on-body delivery system for subcutaneous (SUBQ) administration with intravenous (IV) ravulizumab in eculizumab-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH)., Methods: Patients with PNH received SUBQ ravulizumab (n = 90) or IV ravulizumab (n = 46) during the 10-week randomized treatment period; all patients then received SUBQ ravulizumab during an extension period (< 172 weeks; data cutoff 1 year). Primary endpoint was day 71 serum ravulizumab trough concentration (C trough ). Secondary endpoints were ravulizumab C trough and free C5 over time. Efficacy endpoints included change in lactate dehydrogenase (LDH), breakthrough hemolysis (BTH), transfusion avoidance, stabilized hemoglobin, and Treatment Administration Satisfaction Questionnaire (TASQ) score. Safety, including adverse events (AEs) and adverse device effects (ADEs), was assessed until data cutoff., Results: SUBQ ravulizumab demonstrated PK non-inferiority with IV ravulizumab (day 71 SUBQ/IV geometric least-squares means ratio 1.257 [90% confidence interval 1.160-1.361; p < 0.0001]). Through 1 year of SUBQ administration, ravulizumab C trough values were > 175 μg/mL (PK threshold) and free C5 < 0.5 μg/mL (PD threshold). Efficacy endpoints remained stable: mean (standard deviation, SD) LDH percentage change was 0.9% (20.5%); BTH events, 5/128 patients (3.9%); 83.6% achieved transfusion avoidance; 79.7% achieved stabilized hemoglobin. Total TASQ score showed improved satisfaction with SUBQ ravulizumab compared with IV eculizumab (mean [SD] change at SUBQ day 351, - 69.3 [80.1]). The most common AEs during SUBQ treatment (excluding ADEs) were headache (14.1%), COVID-19 (14.1%), and pyrexia (10.9%); the most common ADE unrelated to a device product issue was injection site reaction (4.7%). Although many patients had ≥ 1 device issue-related ADE, full SUBQ dose administration was achieved in 99.9% of attempts., Conclusions: SUBQ ravulizumab provides an additional treatment choice for patients with PNH. Patients may switch to SUBQ ravulizumab from IV eculizumab or ravulizumab without loss of efficacy., Trial Registration: NCT03748823., (© 2022. The Author(s).)

Background: Augmented glycolysis in cancer cells is a process required for growth and development. The Warburg effect provides evidence of increased glycolysis and lactic acid fermentation in cancer cells. The lactate end-product of glycolysis is receiving growing traction for its role as a cell signalling molecule. Ovarian cancer (OvCa) is also characterised by altered glucose metabolism. We aim to explore circulating lactate levels in patients with high-grade serous OvCa (HGSOC) and to elucidate the expression of the lactate receptor hydroxycarboxylic acid receptor 1 (HCAR1) in OvCa. Methods: HCAR1 expression was detected in patient biopsy cores using immunohistochemistry, while lactate was measured from whole blood with a Biosen-C line clinic measuring system. Results: We noted significantly elevated lactate levels in OvCa patients (4.3 ± 1.9 mmol/L) compared with healthy controls (1.4 ± 0.6 mmol/L; p < 0.0001), with an AUC of 0.96. The HCAR1 gene is overexpressed in OvCa compared to healthy controls (p < 0.001). Using an OvCa tissue microarray (>75% expression in 100 patients), high protein expression was also recorded across all epithelial OvCa subtypes and ovarian normal adjacent tissue (NAT). Conclusions: Lactate monitoring is a simple, cost-efficient test that can offer point-of-care results. Our data suggest that the potential of circulating lactate as a screening biomarker in OvCa merits further research attention.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common type of inherited cystic kidney disease. The feasibility of whole‑exome sequencing (WES) to obtain molecular diagnosis of ADPKD is still in question as previous studies showed conflicting results. Utilizing WES on a patient with ADPKD, standard bioinformatics pipeline demonstrated no pathogenic variant in the genes of interest. By visualizing read alignments using the Integrative Genomics Viewer, a region with atypical alignment of numerous soft‑clipped reads at exon 45 of polycystin 1, transient receptor potential channel interacting ( PKD1 ) gene was demonstrated. A total of four visual inspection steps were outlined to assess the origin of these soft‑clipped reads as strand bias during capture, poor mapping, sequencing error or DNA template contamination. Following assessment, the atypical alignment at PKD1 was hypothesized to be caused by an insertion/deletion mutation. Sanger sequencing confirmed the presence of a novel 20‑bp insertion in PKD1 (NM&#95;001009944.3; c.12143&#95;12144insTCC​CCG​CAG​TCT​TCC​CCG​CA; p.Val4048LeufsTer157), which introduced a premature stop codon and was predicted to be pathogenic. The present study demonstrated that WES could be utilized as a molecular diagnostic tool for ADPKD. Furthermore, visual inspection of read alignments was key in identifying the pathogenic variant. The proposed visual inspection steps may be incorporated into a typical WES data analysis workflow to improve the diagnostic yield.

Background: The BUB 1 mitotic checkpoint serine/threonine kinase B (BUB1B) gene encodes a key protein in the mitotic spindle checkpoint, which acts as a surveillance mechanism, crucial for the maintenance of the correct chromosome number during cell deviation. Mutations of BUB1B gene are linked to mosaic variegated aneuploidy 1 (MVA1) syndrome, a rare autosomal recessive disorder characterized by widespread mosaic aneuploidies, involving different chromosomes and tissues. MVA1 is clinically characterized by intrauterine growth restriction, post-natal growth retardation, and severe neurologic impairment including microcephaly, developmental delay/intellectual disability, epileptic seizures, and generalized hypotonia. Malignancies are also serious sequelae associated with the disorder. We reported on a case of two-year-old Italian girl with MVA1 who shows severe neurologic impairment, microcephaly and epileptic seizures., Materials and Methods: Clinical data collection and genetic diagnosis of the patient were assessed. Mutational analysis covers the chromosomal microarray analysis, the gene methylation pattern studied using the methylation-specific multiplex ligation-dependent probe amplification, and the family-based Whole Exome Sequencing (WES). A literature research based on reported cases of MVA and premature chromatid separation was also included., Results: Karyotyping has revealed 12% of mosaics in the patient who carries a novel variant in BUB1B gene (c.2679A > T, p.Arg893Ser) detected by WES. Thirty-one cases of MVA1 including the present report, and four prenatally diagnosed cases with MVA1 were selected and inspected., Conclusion: Clinical and genetic findings reported in the girl strongly suggest a new MVA1 genotype-phenotype correlation and lead to a reappraisal of a severe syndrome. Diagnosis and in-depth follow-up provided worthwhile data., (© 2022. The Author(s).)

Background: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS following initiation of vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), and overall survival (OS)., Materials and Methods: Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. MGMT promoter methylation was assessed on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using methylation sensitive restriction enzyme-quantitative PCR (MSRE-qPCR). Survival was estimated by the Kaplan-Meier method., Results: A total of 20 ES patients underwent MGMT promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated MGMT , whereas the remaining (15; 75%) had unmethylated promoter. Five (25%) had objective response to IT, with no observed difference by promoter methylation (p = 0.76). Median PFS from initiation of IT for methylated vs . unmethylated MGMT patients was 4.9 and 1.2 months, respectively, p = 0.69. Median PFS from date of initiation of VDC-IE was significantly superior in the methylated group; 27.8 vs . 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group., Conclusion: MGMT -promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated MGMT predicted significantly superior PFS following initiation of the standard VDC-IE protocol., Competing Interests: Conflict of interest None to declare., (© 2022 Greater Poland Cancer Centre.)

Hyperuricemia remains the most prevalent cause of gout. Gout patients present with joint inflammation and uric acid crystals deposition manifesting as tophi. The association of gout with increased risk of insulin resistance, diabetes, metabolic disorders, increased cardiometabolic risk, and kidney disease is well established. These factors influence the treatment plan, and current treatment options have limited cardiovascular risk reduction. So the need for novel treatments with a broad range of coverage for the complications is warranted. Sodium-glucose co-transporter 2 inhibitors are novel drugs approved for treating type-2 diabetes. They prevent glucose reabsorption and lower serum uric acid levels. Recently few studies have studied their association with reducing the risk of gout. They may help address the gout related complications through their recorded benefit with weight loss, improved insulin resistance, and cardiovascular benefits in recent studies. . SGLT2-Is may be useful to reduce the risk of gout in individuals with type 2 diabetes. Limited literature is available on the safety and efficacy of these novel antidiabetic drugs in patients with gout. This review is aimed to summarize the current knowledge on the role and effectiveness of novel antidiabetic medication as an early therapeutic option in gout patients., Competing Interests: Conflict of interests: The authors declare no conflicts of interest., (Copyright © 2022, Somagutta MKR et al., Applied Systems and Discoveries Journals.)

CD38 was first discovered as a T-cell antigen and has since been found ubiquitously expressed in various hematopoietic cells, including plasma cells, NK cells, B cells, and granulocytes. More importantly, CD38 expression levels on malignant hematopoietic cells are significantly higher than counterpart healthy cells, thus presenting itself as a promising therapeutic target. In fact, for many aggressive hematological cancers, including CLL, DLBCL, T-ALL, and NKTL, CD38 expression is significantly associated with poorer prognosis and a hyperproliferative or metastatic phenotype. Studies have shown that, beyond being a biomarker, CD38 functionally mediates dysregulated survival, adhesion, and migration signaling pathways, as well as promotes an immunosuppressive microenvironment conducive for tumors to thrive. Thus, targeting CD38 is a rational approach to overcoming these malignancies. However, clinical trials have surprisingly shown that daratumumab monotherapy has not been very effective in these other blood malignancies. Furthermore, extensive use of daratumumab in MM is giving rise to a subset of patients now refractory to daratumumab treatment. Thus, it is important to consider factors modulating the determinants of response to CD38 targeting across different blood malignancies, encompassing both the transcriptional and post-transcriptional levels so that we can diversify the strategy to enhance daratumumab therapeutic efficacy, which can ultimately improve patient outcomes.

Objective: To evaluate the magnetic resonance elastography (MRE)-derived liver stiffness measurement (LSM), T1 and T2 relaxation times, and hepatobiliary phase images in patients, who developed sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy., Methods: Thirty-four patients (M/F:22/12) who underwent liver MRI-MRE and received oxaliplatin for colorectal, gastric, and pancreas cancer were included in the study. SOS was diagnosed by Gd-EOB-DTPA-enhanced MRI in 18 patients. MRE-LSM and T1-T2 maps were evaluated. Patients with SOS were grouped according to the amount of reticular hypointensity on the hepatobiliary phase images., Results: The mean MRE-LSM in the patients with SOS was 3.14 ± 0.45 kPa, and the control group was 2.6 ± 0.5 kPa (p = 0.01). The mean-corrected T1 (cT1) relaxation time was 1181 ± 151 ms in the SOS group and 1032 ± 129 ms in the control group (p = 0.005). The mean T2 relaxation time was 50.29 ± 3.6 ms in the SOS group and 44 ± 3.9 ms in the control group (p = 0.01). Parenchymal stiffness values were 2.8 ± 0.22 kPa, 3 ± 0.33 kPa, and 3.65 ± 0.28 kPa in patients with mild, moderate, and advanced SOS findings, respectively (p = 0.002). Although cT1 and T2 relaxation times increased with increasing SOS severity, no statistical significance was found., Conclusions: We observed increased MRE-LSM in patients with SOS after chemotherapy compared to control group. T1 and T2 relaxation times were also useful in diagnosing SOS but were found inadequate in determining SOS severity. MRE is effective in diagnosing SOS and determining SOS severity in patients who cannot receive contrast agents, and it may be useful in the follow-up evaluation of these patients., (© 2022. The Author(s).)

Objectives: Primary objective was to explore experiences of female residents of Obstetrics and Gynecology (OB/GYN) regarding lapses in patient safety (PS) while secondary objective was to explore factors hampering or favouring improvement of PS in OB/GYN., Methods: In this qualitative narrative study carried out in OB/GYN department of Combined Military Hospital (CMH) Lahore for six months from 1 st April to 30 th September 2021, six fourth-year residents were asked to write narratives of their personal experiences of medical error (witnessed or committed) in detail and reflect on those experiences, which were then transcribed. Code labels and themes were assigned manually. Interpretation of these themes was done after thematic content analysis., Results: Six, fourth-year female residents with a mean age of 28.6±1.8 participated in the study. Two main themes with sub-themes were identified: 1) Challenges in patient safety (Personal challenges, Workplace challenges, Barriers to PS), 2) Lessons learnt from experiences (Self-improvement and; Promotion of patient safety culture). Heavy workload with long working hours, lack of communication and teamwork, lack of experience and inadequate supervision were major factors involved in PS lapses experienced by residents., Conclusion: Incidents of Patient Safety (PS) lapses had a strong impact on the emotional and professional life of residents. Formal PS training with improvement of working conditions may help promote PS culture., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)